近日，美国FDA批准Rexulti(brexpiprazole)治疗精神分裂症成年患者，及作为一种辅助治疗药物添加到抗抑郁药物中治疗重度抑郁症（MDD）成年患者。
精神分裂症是一种慢性、严重并令人致残的脑部疾病，其影响大约百分之一的美国人。通常情况下，症状最早见于不到30岁的成年中当中，包括听到声音，认为别人正在读懂他们的心思或控制他们的思想及多疑或孤僻。
FDA的药品评价和研究中心精神产品部门主任说：“精神分裂症和重性抑郁症可以能致残和可能大大地破坏天-天活动，”“药物对每个人影响不同所以重要的是对精神疾病患者可得到各种各样治疗选择。”
批准日期：2015年7月10日；公司：大冢制药和H.Lundbeck A/S
REXULTI（布瑞哌唑[brexpiprazole]）片剂，口服使用
美国最初批准：2015年
警告：患有与痴呆症有关的精神病患者的老年人死亡人数增加;并且自杀的想法和行为请参见完整的BOXED警告的完整预定信息。
用抗精神病药治疗的老年痴呆相关精神病患者死亡风险增加。 REXULTI未被批准用于治疗痴呆相关精神病患者。
抗抑郁药可增加24岁及以下患者的自杀念头和行为风险。
监测临床恶化和自杀念头和行为的出现。
REXULTI的安全性和有效性尚未在儿科患者中建立。
最近的重大变化
警告和注意事项，病态赌博和其他强迫行为：02/2018
作用机制
brexpiprazole在治疗重度抑郁症或精神分裂症中的作用机制尚不清楚。然而，brexpiprazole的功效可以通过5-羟色胺5-HT 1A和多巴胺D 2受体的部分激动剂活性和5-羟色胺5-HT 2A受体的拮抗剂活性的组合来介导。
适应症和用法
REXULTI是一种非典型抗精神病药，用于：
用作抗抑郁药治疗重度抑郁症（MDD）的辅助治疗
治疗精神分裂症
剂量和给药
每天使用或不使用食物进行REXULTI一次
适应症          开始剂量         推荐剂量    最大剂量
MDD         0.5毫克/天或1毫克/天 2毫克/天    3毫克/天
精神分裂症       1毫克/天       2至4毫克/天  4毫克/天
中度至严重肝功能损害（Child-Pugh评分≥7）：对于精神分裂症患者，MDD患者每日一次最大推荐剂量为2 mg，每日一次为3 mg。
中度，严重或终末期肾功能损害（CLcr <60 mL /分钟）：对于精神分裂症患者，MDD患者每日一次最大推荐剂量为2 mg，每日一次3 mg。
已知的CYP2D6差的代谢产物：将通常的剂量减少一半。
剂量形式和强度
片剂：0.25mg，0.5mg，1mg，2mg，3mg和4mg。
禁忌症
已知对REXULTI或其任何组分的超敏反应。
警告和注意事项
老年痴呆相关精神病患者的脑血管不良反应：脑血管不良反应发生率增加（例如中风，短暂性脑缺血发作）。
神经阻滞性恶性综合症：立即停药并密切监测。
迟发性运动障碍：如果临床适当，则停用。
代谢变化：监测高血糖/糖尿病，血脂异常和体重增加。
病理性赌博和其他强迫行为：考虑减少剂量或停药。
白细胞减少症，中性粒细胞减少症和粒细胞缺乏症：对已有低白细胞计数（WBC）或白细胞减少或中性粒细胞减少症史的患者进行全血细胞计数（CBC）。如果在没有其他致病因素的情况下发生WBC临床显着下降，则考虑停止REXULTI。
直立性低血压和晕厥：监测心率和血压，并警告患有已知心血管或脑血管疾病的患者，以及脱水或晕厥的风险。
癫痫发作：对有癫痫发作史或癫痫发作阈值降低的病人慎用。
不良反应
最常见的不良反应是：
MDD：体重增加和静坐不能（≥5％，至少是安慰剂的两倍）
精神分裂症：体重增加（≥4％，至少是安慰剂的两倍）
要报告疑似不良反应，请致电1-800-438-9927联系Otsuka America Pharmaceutical，Inc。或致电1-800-FDA-1088（www.fda.gov/medwatch）联系FDA。
药物相互作用
因素                                            REXULTI的剂量调整
强CYP2D6 *或CYP3A4抑制剂                        给予常用剂量的一半
具有强/中等CYP3A4抑制剂的强/中等CYP2D6          给予常用剂量的四分之一
已知的CYP2D6差的代谢产物服用强/中等CYP3A4抑制剂 给予常用剂量的四分之一
强CYP3A4诱导剂                     将常用剂量加倍，并根据临床反应进一步调整
当施用强CYP2D6抑制剂（例如帕罗西汀，氟西汀）时，可以在MDD患者中不施用剂量调整施用REXULTI。
用于特定人群
怀孕：在妊娠晚期接触的新生儿可能会引起锥体外系和/或戒断症状。
包装提供/存储和处理
提供
REXULTI（brexpiprazole）片剂的一面有标记，有以下强度和包装配置（见表13）：
REXULTI平板电脑的封装配置
REXULTI 0.25MG TAB 30 BREXPIPRAZOLE OTSUKA AMERICA 59148003513 
REXULTI 0.5MG TAB 30 BREXPIPRAZOLE OTSUKA AMERICA 59148003613 
REXULTI 1MG TAB 30 BREXPIPRAZOLE OTSUKA AMERICA 59148003713 
REXULTI 2MG TAB 30 BREXPIPRAZOLE OTSUKA AMERICA 59148003813 
REXULTI 3MG TAB 30 BREXPIPRAZOLE OTSUKA AMERICA 59148003913 
REXULTI 4MG TAB 30 BREXPIPRAZOLE OTSUKA AMERICA 59148004013
存储
将REXULTI片剂储存在20°C至25°C（68°F至77°F）; 允许偏移15°C至30°C（59°F至86°F）[见USP受控室温]。
完整说明资料附件：
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2d301358-6291-4ec1-bd87-37b4ad9bd850
REXULTI(brexpiprazole)tablets, for oral use
General Information
Rexulti (brexpiprazole) is an atypical antipsychotic.
Rexulti is specifically indicated for the adjunctive treatment of major depressive disorder and the treatment of schizophrenia.
Rexulti is supplied as a tablet for oral administration. The recommended dose is as follows:
Major depressive disorder: the recommended starting dose is 0.5 mg or 1 mg once daily, taken orally with or without food. Titrate to 1 mg once daily, then up to the target dosage of 2 mg once daily. Dosage increases should occur at weekly intervals based on the patient’s clinical response and tolerability. The maximum recommended daily dosage is 3 mg. Periodically reassess to determine the continued need and appropriate dosage for treatment.
Schizophrenia: the recommended starting dose is is 1 mg once daily on Days 1 to 4, taken orally with or without food. The recommended target dosage is 2 mg to 4 mg once daily. Titrate to 2 mg once daily on Day 5 through Day 7, then to 4 mg on Day 8 based on the patient’s clinical response and tolerability. The maximum recommended daily dosage is 4 mg. Periodically reassess to determine the continued need and appropriate dosage for treatment.
Clinical Results
FDA Approval
Adjunctive treatment for Major Depressive Disorder:
The efficacy of Rexulti in the adjunctive treatment of major depressive disorder (MDD) was eva luated in two 6-week, double-blind, placebo-controlled, fixed-dose trials of adults meeting DSM-IV-TR criteria for MDD, with or without symptoms of anxiety, who had an inadequate response to prior antidepressant therapy (1 to 3 courses) in the current episode and who had also demonstrated an inadequate response throughout the 8 weeks of prospective antidepressant treatment. In Study 228 (Study 1) subjects were randomized to Rexulti 2 mg once a day or placebo. In Study 227 (Study 2) subjects were randomized to Rexulti 1 or 3 mg once a day or placebo. For subjects randomized to Rexulti, all subjects initiated treatment at 0.5 mg once daily during Week 1. At Week 2, the Rexulti dosage was increased to 1 mg in all treatment groups, and either maintained at 1 mg or increased to 2 mg or 3 mg once daily, based on treatment assignment, from Week 3 onwards. The dosages were then maintained for the 4 remaining weeks. The primary endpoint was change from baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item clinician-related scale used to assess the degree of depressive symptomatology, with 0 representing no symptoms, and 60 representing worst symptoms. At randomization, the mean MADRS total score was 27. In both studies adjunctive brexpiprazole showed greater improvement than adjunctive placebo in MADRS total score at Week 6 in the efficacy population per final protocol in Study 1 (2mg+ADT [N=175]: -3.21, p=0.0002), and in Study 2 (1mg+ADT [N=211]: -1.30, p=0.0737; 3mg+ADT [N=213]: -1.95, p=0.0079). Similar results were observed for the efficacy population in both studies. The completion rate was high (>90%) and comparable across brexpiprazole and placebo groups.
Schizophrenia:
The efficacy of Rexulti in the treatment of adults with schizophrenia was demonstrated in two 6-week, randomized, double-blind, placebo-controlled, fixed-dose clinical trials in subjects who met DSM-IV-TR criteria for schizophrenia. In both studies, Study 231 (Study 3) and Study 230 (Study 4), subjects were randomized to Rexulti 2 or 4 mg once per day or placebo. Subjects in the Rexulti groups initiated treatment at 1 mg once daily on Days 1 to 4. The Rexulti dosage was increased to 2 mg on Days 5 to 7. The dosage was then either maintained at 2 mg once daily or increased to 4 mg once daily, depending on treatment assignment, for the 5 remaining weeks. The primary efficacy endpoint of both trials was the change from baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) total score. In one study, brexpiprazole 4mg and 2mg demonstrated greater improvement than placebo in the primary endpoint of change from baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (4mg: -19.65, p=0.0006 and 2mg: -20.73, p=<0.0001 vs. placebo -12.01; 0.25mg was similar to placebo -14.90). In the other study, brexpiprazole 4mg showed improvement over placebo in the primary endpoint of PANSS Total Score from baseline to Week 6 (-20.0 vs. -13.5, p=0.0022), while the 2mg (-16.6) and 1mg (-16.9) doses showed numeric improvement versus placebo (-13.5, p>0.05).
Side Effects
Adverse effects associated with the use of Rexulti may include, but are not limited to, the following:
akathisia
weight gain
Rexulti comes with a black box warning of increased mortality in elderly patients with dementia-related psychosis; and a potential risk in the increase of the risk of suicidal thoughts and behaviors in patients aged 24 years and younger.
Mechanism of Action
Rexulti (brexpiprazole) is an atypical antipsychotic. The mechanism of action of brexpiprazole in the treatment of major depressive disorder or schizophrenia is unknown. However, the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors.